Alginate oligomers for use in overcoming multidrug resistance in bacteria

Abstract

The invention provides a method of overcoming resistance to at least one antibiotic in a multidrug resistant bacterium, said method comprising contacting said bacterium with an alginate oligomer together with the antibiotic. The multidrug resistant bacterium may be on an animate or inanimate surface and both medical and non-medical uses and methods are provided. In one aspect the invention provides an alginate oligomer for use together with at least one antibiotic in treating a subject infected, suspected to be infected, or at risk of infection, with a multidrug resistant bacterium to overcome resistance to the antibiotic in said multidrug resistant bacterium. In another aspect the method can be used to combat contamination of a site with multidrug resistant bacteria, e.g. for disinfection and cleaning purposes.

Description

FIELD OF THE INVENTION[0001]The present invention relates to alginate oligomers for use together with (or in combination or conjunction with) an antibiotic to overcome (in the sense of reducing) resistance to the antibiotic in a multidrug resistant (MDR) bacterium. Whilst a principal and important use of the present invention is in the treatment or prevention of bacterial infections with MDR bacteria, namely a medical use, the invention also encompasses such use of alginate oligomers in non-medical settings (e.g. in vitro). The invention thus provides alginate oligomers for use together with (or in combination or conjunction with) an antibiotic for the treatment or prevention of an MDR bacterial infection in a subject, or for combating MDR resistant bacteria in vitro (for example in combating the microbial contamination (i.e. colonisation) of an abiotic site with MDR bacteria).BACKGROUND OF THE INVENTION[0002]Ever since antibiotics were first used it was appreciated that bacteria co...

AI Technical Summary

Benefits of technology

[0032]It has now been found that alginate oligomers can be used to overcome antibiotic resistance and render bacteria that are MDR (resistant to multiple classes of antibiotics) susceptible to antibiotics (more specifically susceptible to antibiotic(s) to which they are resistant) and so the use of alginate oligomers together with antibiotics constitutes a highly effective approach to the combat of contamination and infections caused by MDR bacteria.

Problems solved by technology

Generally intrinsic resistance may be seen to a particular type or class of antibiotic, but the number of different antibiotic classes to which resistance is seen is usually restricted.

For instance, this may involve changes in the structure of the target of the antibiotic that reduces the sensitivity of the target to the antibiotic.

This problem is compounded by the presence of intrinsic resistance to many of the β lactam antibiotics.

They represent an emerging problem because of the increasing prevalence of strains with β-lactam antibiotic resistance due to the spread amongst Providencia populations of extended-spectrum beta-lactamase (ESBL).

Providencia infections with antimicrobial resistance patterns are increasing and ESBL-positive P. stuartii is an increasing problem in hospitalized patients.

Of concern is the fact that many Acinetobacter strains appear to be multidrug resistant, thus making the combat of Acinetobacter infections and contamination difficult.

The presence of invasive devices, in particular respiratory support equipment and urinary catheters, increase the likelihood of nosocomial infection with Klebsiella species.

Problematically, resistance of Klebsiella species to antibiotics is increasing.

Unfortunately, the number of antibiotics available to physicians is finite and has remained largely unchanged for many years.

Bacteria resistant to multiple antibiotics are therefore proportionately more difficult to treat.

An alginate molecule can comprise some or all of these structures and such structures might not be uniformly distributed throughout the polymer.